Field of the Invention
This invention is directed to micronized placental compositions comprising micronized placental components and optionally a filler, wherein a biologically compatible chelator moiety is conjugated to a component of the composition. This invention further comprises such compositions having pharmacologically active metal ions reversibly bound to the chelating moiety.
State of the Art
Placental tissue components such as isolated amnion and chorion as well as laminates thereof are known in the art for use as wound coverings and to promote wound healing. Typically, placental tissue is harvested after an elective Cesarean surgery. The placenta is composed of an amniotic membrane which has two primary layers of tissue, amnion and chorion. Amnion tissue is the innermost layer of the amniotic sac and in direct contact with the amniotic fluid. The amniotic sac contains the amniotic fluid and protects the fetal environment. Histological evaluation indicates that the membrane layers of the amnion consist of a single layer of epithelium cells, thin reticular fibers (basement membrane), a thick compact layer, and a fibroblast layer. The fibrous layer of amnion (i.e., the basement membrane) contains collagen types IV, V, and VII, and cell-adhesion bioactive factors including fibronectin and laminins. The amnion so recovered is commercially used in wound grafts which protect the wound and induce healing.
In addition to such beneficial uses, amnion has been found to act as a stem cell recruiter as provided in U.S. Patent Application Publication No. 2014/0106447, which is incorporated herein by reference in its entirety.
U.S. Patent Application Publication 2013/0344162 describes micronized placental tissue compositions and methods of making and using the same. U.S. patent application Ser. No. 13/903,878 describes biologically compatible polymer-chelator conjugates and methods of making and using the same. These references are incorporated herein by reference in their entirety.
Koob et al. have described methods of producing nordihydroguaiaretic acid (NDGA) polymerized and cross-linked collagen fibers for various biomedical applications, some with tensile strengths similar to that of natural tendon (e.g., about 91 MPa). See, for example, Koob and Hernandez, Material properties of polymerized NDGA-collagen composite fibers: development of biologically based tendon constructs, Biomaterials 2002 January; 23 (1): 203-12; and U.S. Pat. No. 6,565,960, the contents of which are hereby incorporated by reference as if recited in full herein.